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Chapter 6: Discussion, conclusion and recommendations

Nuclear Monitor Issue: 
Medical radioisotopes

Until 2007 there was an almost uninterrupted supply of cheap subsidized reactor-produced isotopes, there was no need to search for alternatives. From January 2007 until February 2010  there has been at least six periods of serious disruption to supplies and since February 2010 after the shut-down of the HFR in Petten the world experiences the most serious period of medical isotopes shortages. Only in Canada the first disruptions were followed by serious debates on how to secure the domestic supply of radiopharmaceuticals in the nearby future and the future.

6.1 Discussion
The development of accelerator-based production of medical isotopes has always been thwarted in favor of the production with nuclear reactors. Policymakers are opting for research reactors, because they offer large scale production of medical isotopes. The continued disruptions, however, have proven that the reactor method is not safe and secure. And why should the isotopes production be dependent on a few worldwide monopolists? Cyclotrons offer the possibility to produce hospital-based medical isotopes.

Clinical and biomedical research communities in Canada have begun to look for alternative ways to produce technetium-99m needed for vital clinical procedures and also to explore the potential of alternative medical isotopes to replace technetium as the radiopharmaceutical label in clinical practice. Developments in this field can be observed in newspaper articles.
Let’s take for example a cardiac treatment center. Traditionally, technetium-99m covers about 80% of the isotopes supply used in this discipline. Due to the severe disruptions in the supply of technetium, cardiologists and other medical specialists are searching for the supply of cyclotron-produced isotopes that can be used as an alternative. These include cyclotron-produced technetium or PET isotopes that are performing better than technetium-based modalities. Cardiac PET includes a cyclotron where the lab makes its own medical isotopes. There is no longer any fear for shut downs in the supply of isotopes. PET rubidium-82, generated from cyclotron-produced strontium-82, is a major alternative to technetium. 18FDG-PET imaging tackles large arteries with atherosclerosis. The demand for cyclotron-produced thallium (heart) and iodine (thyroid) is increasing at the expense of reactor-based technetium used in cardiology.77 The same trends can be observed in other medical disciplines among which cancer imaging and therapy. Also in the Netherlands medical centers have been started to look at other sources to secure their isotopes supply as a consequence of the ongoing crisis. More and more medical disciplines switch over to cyclotrons. Recently such decisions were made in Dutch hospitals in Alkmaar and Den Bosch.

Today Canada is frontrunner in the development of isotopes production by accelerators.
The Canadian subatomic physics laboratory TRIUMF  (TRI University Meson Facility) is involved in projects for accelerator-based production of technetium-isotopes and the production of gallium compounds for use as radiopharmaceuticals as alternatives to existing technetium-radiopharmaceuticals. The molybdenum-99 manufacturing method of TRIUMF involves the use of  a highly intense photon beam. Instead of thermal neutrons as in the reactor, electrons are used to irradiate the target material. Instead of high-enriched uranium targets as in reactors (vulnerable for nuclear proliferation), natural uranium is used as target material. In addition, the production of the positron emitter technetium-94 is proposed. This means that the produced technetium-isotopes can make use of the existing technetium-based radiopharmaceuticals for PET as well as SPECT imaging. The second project is the production of  gallium-68 (68Ga) and gallium-67 (67Ga) as alternatives to the 99mTc radiopharmaceuticals. A benefit of this alternative is that 67Ga will allow users the option of imaging using SPECT while 68Ga is a generator produced PET isotope that enables access to these agents in facilities without cyclotrons. This project is in co-operation with the Canadian partner MDS-Nordion, a leading global provider of medical isotopes and radiopharmaceuticals in molecular medicine.78

Meanwhile, another Canadian company - Advanced Cyclotron Systems, Inc. (ACSI) - a world leader in the design and manufacturing of cyclotron equipment, submitted a proposal for a National Cyclotron Network to Produce Medical Isotopes that would fulfill all the Canadian 99mTc needs. ACSI’s TR24 cyclotron, the only 24 MeV cyclotron of its kind in the world, can produce PET and SPECT isotopes including 99mTc, 123I and 68Ge. ACSI is proposing the direct production of 99mTc on TR-24 cyclotrons as suggested by the Canadian Expert Review Panel on Medical Isotope Production. “A national network of eight strategically placed cyclotrons provides both a scalable and reliable source of isotopes and is financially self-supporting following a modest initial capital investment. Leveraging existing cyclotron technology and distribution centers, the network can begin operations within eighteen months (from January 2009) and would meet the entire Canadian medical isotope needs in two to three years.” According to their estimations the Canadian demand for 99mTc could be covered by cyclotron production between 2012 and 2014, much earlier as foreseen in the projected time schedule of the expert panel.79

The preparations for the construction of the Pallas reactor are in full swing. Though officially there hasn’t been made a decision yet about the location (Zeeland or Noord-Holland), the board of the Dutch province Noord-Holland has invested €40 million in the construction of the Pallas. For a fraction of this amount Canadian researchers are working on solutions to tackle the urgent problems in the domestic supply of medical isotopes in the nearby future. It is highly likely that Canada will cover its domestic demand for technetium by accelerators in 2014. 

The prices of Canadian built medical cyclotrons are varying from €1,75 million to €4,20 million. Depending on the isotopes production, they can be delivered within a few months or a few year. The construction costs for the Pallas are estimated on €500 million. 

6.2 Conclusions
As described in Chapter 5 seven of the eight most popular reactor-based medical isotopes: molybdenum-99 (99Mo) (or direct production of 99mTc), iodine-131 (131I), phosphorus-32 (32P), , strontium-89 (89Sr), samarium-153 (153Sm), rhenium- 186 (186Re) and lutetium-177 (177Lu) can be easily made in substantial amounts with particle accelerators. The remaining popular reactor-based isotope chromium-51 (51Cr) is not an essential isotope. Similar cyclotron-produced isotopes performs better. Therefore, the widely used slogans of the nuclear industries indicating that reactor-based medical isotopes have been essential for nuclear medicine are false. The question “Is it possible to ban the use of a nuclear reactor for the production of radiopharmaceuticals?” can be answered with a straightforward ‘yes’.

This means that Pallas is not needed for the production of medical isotopes and leads one to suspect that other interests are involved. In the first place these are the commercial interests of Covidien - one of the subsidized monopolists on the global market of reactor-based medical isotopes, and in the second place Nuclear Research Group (NRG), which very much likes to play a major role in the area of nuclear consultancy and nuclear research. In addition it is important for the image of nuclear energy to maintain the coupling with the production of medical isotopes in the public debate and in the public perception.

A decision to develop radiopharmaceuticals with the use of reactors or cyclotrons is simply a choice and not a story of and reactors and accelerators. Cyclotrons are a logical choice. It saves costs and the environment. Moreover, cyclotrons guarantee a safe and secure supply of medical isotopes. Disruptions in the supply of isotopes will be over forever.

6.3 Recommendations
The Canadian researchers who invented the idea of a National Cyclotron Network to Produce Medical Isotopes show the route to a safe and secure production of radioisotopes. It can serve as a model for other nations. It also shows how quickly the transformation of a reactor-based to an accelerator-based production of medical isotopes can take place. If the Dutch government should choose now for such a transformation, like the Canadian government does, the cyclotron-based isotopes could easily cover the Dutch domestic demand for medical isotopes in 2016. Four cyclotrons in Groningen, Utrecht, Rotterdam and Eindhoven are enough to cover the Dutch domestic demand for technetium.

The use of PET/CT with PET isotopes in imaging and therapy presents a better alternative than gamma camera scintigraphy and SPECT with mainly reactor-produced isotopes. The share of reactor-produced medical isotopes will definitely shrink in the coming decades, while the share of PET isotopes is increasing steadily. Policy-makers can anticipate on this trend by making a choice for cyclotron-produced medical isotopes. Besides PET isotopes, this report has shown that all relevant reactor-based isotopes can be made by an accelerator. In addition, investing in cyclotrons also means investing in research for the development of new cyclotron-based pharmaceuticals, just like the current highly popular PET-pharmaceuticals.

77 Canwest News Service 11 July 2009: The new face of nuclear medicine: Radioactive dyes made at an Ottawa heart institute are saving patients from invasive procedures. ine/1781407/story.html
78 TRIUMF Submits Plans for Medical Isotope Alternatives. 17 Sep 2009
79 ACSI Announces New TR-24 Technetium Cyclotron, 10 January 2009

Source: The entire report "Medical radioisotope production without a nuclear reactor" (38 pages) is available at: Contact: Henk van der Keur, Laka Foundation, Ketelhuisplein 43, 1054 RD Amsterdam, The Netherlands.
Tel: +31 20 6168 294